The overall goal of this project is to study the inhibitory effects of cyclic AMP and phosphodiesterase inhibitors on lactose synthesis in the lactating mammary gland and to investigate the potential role of cyclic nucleotides in a physiological regulatory system for the control of milk synthesis and secretion. Three approaches to this problem are being followed with the following specific goals for the next grant year: (1) complete adaption of the floating collagen gel culture technique to guinea pig mammary gland alveolar cells and use this method to study alterations in the cyclic nucleotide systems (including cAMP, cGMP and their respective enzyme systems) during hormone-induced lactogenesis; (2) complete initial studies indicating that cAMP-phosphodiesterase inhibitors, which also inhibit lactose synthesis do not accomplish the latter by blocking glucose uptake and determine whether the observed stimulation of glucose uptake involves active transport or diffusion; and (3) begin ablation studies in rats, including progesterone replacement, to study hormonal dependence of cyclic nucleotide changes in vivo.